Innate Immunity Part II

Question 1

What are the 3 general steps in Complement Activation?

Answer 1

C3 convertase

C5 convertase

MAC attack complex formation

Question 2

Explain the role of C3 convertase?

Answer 2

It cleaves C3 into C3a and C3b.

C3a acts in the inflammatory response

C3b becomes covalently attached to microbe= opsonizon for phag promotion.

C3 convertase binds C3b to become C5 convertase.

Question 3

Explain the role of C5 convertase.

Answer 3

C5 convertase cleaves C5 into C5a and C5b.

C5a promotes changes in permeability of blood vessels.

C5b attaches to microbe and starts the MAC= C6, C7, C8, C9

Question 4

What are the components of the C3 convertase?

Answer 4

C4bC2a

Question 5

Explain the classical pathway steps?

Answer 5

Requires IgM or IgG and

C1q bind Fc region of Ab and then C1r,s perform cleavage.

C3 convertase=C4bC2a

C5 convertase= C4bC2aC3b

MAC

Question 6

Explain the Alternative pathway steps?

Answer 6

Spontaneous/”tickover”

C3 hydrolysis=reason for DAF, CR1, and Fl regulatory proteins

Factor D cleaves Factor B= Ba and Bb

C3bBb bind=then bind C3b of C5 Convertase

Serum protein properdin stabilizes interactions.

C5 convertase

MAC

Question 7

Explain the steps in the Lectin Pathway?

Answer 7

Triggered by mannose-binding lectin binding terminal mannose residues on microbes.

Binding activates MASP1/2=perform proteolytic cleavage.

C3 convertase

C5 convertase

MAC

Question 8

What are Collectins?

Answer 8

Collectins are trimeric proteins with Lectin heads

Soluble effector molecules

SP-A and SP-D are collections

Surfactant proteins that can Opsonin microbes for alveolar macrophages and inhibit growth.

Question 9

What three homologous hexameric proteins can imitate complement?

Answer 9

C1q can when it binds IgM

MBL/MASP1, 2 can when it binds mannose on microbe surface

Ficolin/ MASP1, 2 can when it binds N-acetylglucosamine

Question 10

What are Ficolins?

Answer 10

Plasma proteins that are structurally similar to Collectins but have fibrinogen-type carbohydrate recognition

Molecular ligands are N-acetylgulcosamine and lipoteichoic acid=gram positive

Question 11

What is the common component of all three complement pathways? There is one molecule…

Answer 11

C3b

Question 12

What are the complement regulatory proteins?

Answer 12

DAF= Decay-Accelerating Factor

Blocks C2/C4b interaction or enhance dissociation of C4bC2a

CR1= Complement receptor 1

Enhances dissociation of C4bC2a

F1= Factor 1

With CR1, it cleaves C4b/C3b

Question 13

What are C3a specific functions?

Answer 13

Vasoaction of mast and basophils cells

Question 14

What are C4a specific functions?

Answer 14

Increased chemokinesis

PG/ROS/RNS in neutrophils

Question 15

What C5a specific functions?

Answer 15

Increased IL-I, IL-6

PG

ROS, RNS

Expression of CAMs on monocytes and Macs

Question 16

What are resident Macrophages activated by?

Answer 16

LPS by TLR

IFN-Gamma binds from NK or T-Cells binds cytokine receptor

Complement fragment

Question 17

What are resident macrophage functional responses?

Answer 17

Acute Inflammation via TNF, IL-1= leads to IL-6,

Also IL-12

ROS/NOS

phage

Question 18

Understand local vs. systemic action of cytokines in inflammation.

Answer 18

Systemic TNF can cause

Septic shock, decreased cardiac function, thrombosis and capillary leak, metabolic abnormalities due to insulin resistance.

Question 19

What are Acute Phase Proteins?

Answer 19

Plasma proteins belonging to the pentraxin family

Examples are C-reactive protein (CRP) and Serum Amyloid P (SAP)

Expression in the liver via IL-6/IL-1 induction

Question 20

What do E-reactive protein and serum amyloid P recognize?

Answer 20

CRP=phosphoric hotline

SAP=phosphatidylethanolamine

Can activate complement by binding C1q

Question 21

What are the three complement system cascades? And what are they composed of?

Answer 21

The Classical Pathway

The Alternative Pathway

The Lectin Pathway

They composed of plasma proteins expressed in the liver that at as proteolytic proteases.